Transient Global Amnesia

TGA, once observed, is a remarkable condition. Its sufferers (for lack of a better word) lose the ability to form memories for up to 24 hours. They are marked by their propensity to repeat the same questions over and over again. They recover with only loss of memory for the discrete period of time in which they were impaired. The neuroimaging case cited below records bilateral hippocampal lesions that corresponded to the period of impairment. This included hyperintensity on FLAIR, restricted diffusion, and a SPECT scan showing hypoperfusion of bilateral hippocampi. Not all cases are associated with MRI changes but these studies seem to support the idea that hypoperfusion of the hippocampi without infarct causes the syndrome.

Di Filippo M, Calabresi P. Ischemic bilateral hippocampal dysfunction during transient global amnesia. Neurology 69;5:493.

Musical Automatisms

A few cases were collected together to see if ictal humming or singing had an anatomic correlate. Ictal singing seemed to correlate with right prefrontal seizures. Humming arose from temporal seizures. Singing seems to lateralize more to the right including "the superior temporal gyrus, the inferior central operculum, and particularly the inferior frontal gyrus."

Bartolomei F, et al. Clinical and Anatomic Characteristics of Humming and Singing in Partial Seizures. Neurology 69;5:490-2.

Carbamazepine

This is an effective medication for trigeminal neuralgia (for which it was originally approved) and partial and generalized seizures. It has the characteristic of possibly worsening absence and myoclonic seizures.

A well-known, dangerous, but rare complication is a drug rash which can progress to Stevens-Johnson Syndrome. In its most fulminant form, it can be fatal. This side effect can occur anytime during its administration. Toxic hepatitis and leukopenia may also occur. Since carbamazepine has other uses, it may be chosen despite its side effects, with the idea that it is treating more than just seizures.

Carbamazepine is also a medication in which levels can be checked. This can be helpful when a patient taking the drug presents with somnolence, dysarthria, and ataxia, and in addition on exam has fine nystagmus and asterixis. This presentation corresponded to a level of 20 (normal 8-12). How the level became this high is unknown.

Parkinson's Disease: Autonomic Symptoms

Parkinson's Disease with its four cardinal symptoms of tremor, rigidity, bradykinesia, and postural instability is becoming increasingly associated with dysautonomia. In fact, "autonomic complaints such as constipation may predae the motor signs of PD." Also, these nonmotor symptoms of PD are associated with significant decrease in quality of life. To date, no tested therapies are available to treat these autonomic symptoms.

Shannon KM. Dopamine: So "last century". Neurology 2007;69:329-332.

Basal Ganglia Circuits

The concepts of the direct pathway and indirect pathway take up a day of medical school neuroscience courses. They usually follow a discussion of the four dopamine pathways: the nigrostriatal, mesocortical, mesolimbic, and tuberoinfundibular.

These circuits were recently featured in the journal Neurology.

Benarroch E. Endocannabinoids in basal ganglia circuits. Neurology 2007;69:306-309.

In the diagram featured in that article the only variation in the above schematic is the contribution of the substantia nigra pars compacta. According to the article, "dopaminergic inputs from the SNc modulate the activity of these pathways, exerting a net excitatory effect on the direct and a net inhibitory effect on the indirect pathway."

Dr. Benarrach says it better than I could: in the direct pathway "striatal neurons elicit a phasic inhibition of the GPi/SNr, leading to disinhibition of the thalamus and brainstem motor areas". The indirect pathway is explained thus: "since the GPe tonically inhibits the STN, activation of the indirect pathway disinhibits the STN. The resulting increase in STN activity leads to an increase in inhibitory output from the GPi/SNr, resulting in inhibition or termination of motor programs."

Justice Roberts has a Seizure

On July 31, 2007, the New York Times published an article of contradictory opinions in regards to the Chief Justice's July 30 seizure.

Early in the article his epilepsy is characterized as idiopathic while nearer to the end of the article one quoted physician calls it cryptogenic. There is obvious disagreement about whether he should receive antiepileptics.

The Chief Justice by definition has epilepsy, probably cryptogenic localization related epilepsy. On July 30 he had a seizure and as epileptics do, he returned to normal afterward. His evaluation, as I am sure he had 14 years ago, should include an MRI and an EEG. Contrary to the Times article, a CT scan does not offer much to his work-up. Both of these tests can be done as an outpatient. As the article states the MRI will probably be normal but it should be done anyway to rule out any intracranial pathology (tumor, stroke, etc.). An EEG can provide some guidance in this situation. If it is normal, then withholding treatment for now would be prudent. If it shows focal slowing or spikes with a normal MRI, then he likely has an underlying abnormality that cannot be found. With an abnormal EEG, the decision would have to be made whether to treat with an antiepileptic drug or wait. With two seizures in 14 years and the specter of medication side effects (including cognitive), hopefully Justice Roberts and his doctors decide to forgo treatment and wait.

Aphasia

Hillis AE. Aphasia: Progress in the last quarter of a century. Neurology 2007;69: 200-213.

This review article surveys the advances in the field, the value of current research, and what has been learned. Aphasia has grown much more complex than that of the Wernicke's and Broca's types. The paper is careful, that is, it is painstakingly nuanced. There are no broad sweeping proclamations. Localization is approximate. Our understanding of aphasia and, moreover, the localization of language, has grown exceedingly complex. Although in medical school, the Wernicke/Broca, receptive/motor, and fluent/dysfluent divide is stressed, the understanding of aphasia is far beyond these easy categories. Without diving in to deeply, a few of the more concrete points are delivered below.

Broca's aphasia, broadly includes "reduced phrase length, impaired melody and articulatory agility, diminished words per minute, and agrammatic sentence production". The different permutations and number of these independent yet intertwined deficits all arise from compromise of blood flow through the superior division of the left middle cerebral artery. The posterior, inferior frontal gyrus is implicated in deficit studies. Aphasias in the Wernicke's spectrum are associated with disruption of blood flow to the inferior division of the left MCA, which supplies the posterior, superior temporal gyrus.

Transcortical aphasias are characterized by intact repitition. Transcortical motor aphasia shares features of Broca's aphasia but with impaired repetition. Associated lesions occur "just anterior or superior to Broca's area, often caused by occlusion of the ACA or "watershed" areas between the ACA and the MCA." Conversely, transcortical sensory aphasia is caused by "lesions surrounding Wernicke's area, in the watershed territories between the MCA and PCA or the PCA territory. Mixed transcortical aphasia is global aphasia with preserved repetition. This syndrome shows dysfunctional cortex surrounding Broca's and Wernicke's areas, "sometimes known as 'isolation of the speech area'".

Conduction aphasia is characterized by phonemic paraphasias.

Pure alexia is usually caused by two lesions, one to the left occipital cortex caused by compromise of the left PCA, and the other to the splenium of the corpus callosum. The splenium lesion disrupts nerve tracts carrying visual information from the right occipital cortex to the left hemisphere language areas. These same two lesions can effect optic aphasia, in which an object cannot be identified by sight but can be identified through tactile cues.

The latter part of the article distinguishes different aphasias by their disrupted cognitive processes. Anecdotal examples of patients with selective aphasias demonstrate the separation of different cognitive functions, and at the same time, their overlap. Consult the article for this to be explained better than I could at this point.